Chapter edited and updated by: Poulami Barman and Sarah Allen
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Protein interaction is crucial for every organism. Most proteins function through interaction with other molecules, and often with other proteins. Enzymes interact with their substrates, inhibitors interact with enzymes, transport proteins interact with structural proteins, hormones interact with receptors – and that’s just a few of the interactions that happen in a cell. Some proteins are composed of more than one polypeptide chain, and the interactions between the different peptides are necessary for the whole protein to function. Since they are so essential, protein-protein interactions are an important topic for scientists to understand.
There are many characteristics of a protein-protein interaction that are important. Obviously, it is important to know which proteins are interacting. In many experiments and computational studies, the focus is on interactions between two different proteins. However, you can have one protein interacting with other copies of itself (oligomerization), or three or more different proteins interacting. The stoichiometry of the interaction is also important – that is, how many of each protein involved are present in a given reaction. Some protein interactions are stronger than others, because they bind together more tightly. The strength of binding is known as affinity. Proteins will only bind each other spontaneously if it is energetically favorable. Energy changes during binding are another important aspect of protein interactions. Many of the computational tools that predict interactions are based on the energy of interactions.
In recent years there has been a strong focus on predicting protein interactions computationally. Predicting the interactions can help scientists predict pathways in the cell, potential drugs and antibiotics, and protein functions. However, it has been an ongoing challenge to decipher those interactions. Proteins are large molecules, and binding between them often involves many atoms and a variety of interaction types, including hydrogen bonds, hydrophobic interactions, salt bridges, and more. Proteins are also dynamic, with many of their bonds able to stretch and rotate leading to different conformations. Therefore, predicting protein-protein interactions requires a good knowledge of the chemistry and physics involved in the interactions.
This chapter discusses the characteristics of protein-protein interactions, how they are determined experimentally, and how they are predicted computationally. It also contains a list of databases where you can explore known and predicted protein interactions. The links above will lead you to the various sections.